EP2678006B1 - Conditionnement de préparations pharmaceutiques solides contenant la substance active trinitrate de glycéryle - Google Patents

Conditionnement de préparations pharmaceutiques solides contenant la substance active trinitrate de glycéryle Download PDF

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Publication number
EP2678006B1
EP2678006B1 EP12706778.3A EP12706778A EP2678006B1 EP 2678006 B1 EP2678006 B1 EP 2678006B1 EP 12706778 A EP12706778 A EP 12706778A EP 2678006 B1 EP2678006 B1 EP 2678006B1
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EP
European Patent Office
Prior art keywords
gtn
preparation according
anyone
preparation
composite film
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Not-in-force
Application number
EP12706778.3A
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German (de)
English (en)
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EP2678006A1 (fr
Inventor
Thomas Zimmeck
Henning Ueck
Julia Gehricke
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G Pohl Boskamp GmbH and Co KG
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G Pohl Boskamp GmbH and Co KG
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Priority to PL12706778T priority Critical patent/PL2678006T3/pl
Publication of EP2678006A1 publication Critical patent/EP2678006A1/fr
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Publication of EP2678006B1 publication Critical patent/EP2678006B1/fr
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D85/00—Containers, packaging elements or packages, specially adapted for particular articles or materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/03—Containers specially adapted for medical or pharmaceutical purposes for pills or tablets
    • A61J1/035—Blister-type containers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules

Definitions

  • the present invention relates to solid pharmaceutical preparations containing volatile active substances in the form of one or more individual doses packaged in specific composite films or blister foils with improved storage stability.
  • the present invention relates to solid pharmaceutical preparations for oral or oromucosal administration containing the active substance glyceryl trinitrate (nitroglycerin, referred to below in abbreviated form as GTN) in the form of pre-dosed granules or in the form of tablets, which are packaged individually in a stick pack, a four-sided sealed pouch or a blister, respectively.
  • GTN active substance that is packaged individually in a stick pack, a four-sided sealed pouch or a blister, respectively.
  • GTN is an active substance which is used in the treatment of attacks of angina pectoris, among other uses, whereby it is especially used in emergency situations, in which the pharmaceutical form must enable a rapid onset of action.
  • sublingual administration has proven very effective with rapid uptake of the active substance and quick relief of symptoms.
  • tablets for oromucosal, i.e. sublingual or buccal administration with rapid onset of action have proven to be especially effective pharmaceutical forms for the outpatient sector.
  • Sprays for sublingual administration which are used to spray the active substance-containing dose underneath the tongue, provide for a direct and rapid application of the dissolved active substance over a large area of the highly resorbent oral mucosa.
  • GTN tablets Up to now commercially available GTN tablets have been filled into glass bottles, which are relatively inert against interactions with the filled product. In addition, they are transparent and protect the contents from external influences. However, due to their low shatter resistence glass containers must be handled with a certain level of caution when carried around by patients. In addition, due to the small size of the tablets the removal of a single tablet can be difficult in an emergency situation, when patients can easily drop the container. Moreover, it is not practical to package individual doses in glass containers and the patients are required to carry around the entire original packaging. For this reason, there is the long felt unmet need for solid and stable pharmaceutical forms for GTN, which are easy for patients to carry around in single-dose form, e.g. in a wallet or jacket pocket, and which simultaneously ensure sufficient stability, simple administration, and rapid onset of action.
  • So-called stick packs or sachets represent an alternative configuration for individual doses, which are becoming increasingly common in the pharmaceutical industry.
  • Stick packs are typically manufactured using composite films consisting of several layers, whereby each individual layer of film performs a specific task (barrier, stiffness, impact resistance, sealing properties, etc.).
  • the barrier layer performs the task of protecting the package contents against substance loss and external contamination.
  • a support layer stabilizes the packaging, enabling it to withstand mechanical stresses, while the sealing layer serves mainly to seal the film package. It is usually made of a thermoplastic polymer and is located on the side of the composite film facing the filling material.
  • Stick packs can be manufactured to contain the pharmaceutical preparation as flowable granules or powder and enable both comfortable transport of the medicinal product as well as simple, easy and reproducible dosing, which is especially significant in emergency situations.
  • the highest possible storage stability is especially critical to enable the patient to carry around a single dose such as, but not limited to a stick pack.
  • carrying it around in the breast pocket of a shirt for example, can subject it to significant temperature increases and associated stress conditions, which may violate the recommended storage conditions for GTN preparations.
  • OFDF oral fast dissolving film
  • GTN has a high affinity for organic materials.
  • organic materials such as cork, cotton, paper, and especially rubber and polyethylene to store GTN-containing tablets must be avoided.
  • Banes Journal of Pharmaceutical Sciences, 57, 1968, 893 ) reported GTN loss in tablets packaged individually in aluminum foil films containing a sealing layer made of polyethylene. Following storage, the tablets were found to have less than 10% of the active substance they originally contained, while the majority of the GTN was found in the sealing layer of the packaging material.
  • Pikal et al. (Journal of Pharmaceutical Sciences, 66, 1977, 1295 ) demonstrate the different, predominantly considerable affinity of various polymers (vinyls, low density polyethylene, high density polyethylene, ionomers) to GTN, which limit their use in primary packaging of GTN compositions.
  • Chen et al. (Database Caplus [online], CAS, Columbus Ohio, US, 2004 , database accession no. 2004:826842 ) investigated the effect of the acrylonitrile-butadiene content in EPDM rubber inhibitor formulations on the inhibitor's performance of resisting nitroglycerin migration using the intermediate layer method. It was demonstrated that the content of acrylonitrile-butadiene in the EPDM rubber inhibitor had significant impact on the inhibitors performance.
  • a primary packaging material suitable for the production of individual doses e.g. in the form of stick packs, must be flexible and sufficiently stable in order to avoid being destroyed during transport.
  • the packaging material must be inert and impervious to the active substance as well as to impurities, which can reach the preparation from the outside.
  • a series of materials is available in the form of composite films for the production of stick packs, sachets and blisters.
  • aluminum composite films are especially suited for the packaging of pharmaceutical preparations which should be protected from external influences. They exhibit the following layer structure:
  • the surface of the aluminum film coming into contact with the filling material is provided with a sealing medium.
  • Sealing materials differ in certain physico-chemical properties, e.g. the softening temperature and a possible interaction with the components of the pharmaceutical preparation. Available materials include composite films with polyethylene (PE), polypropylene (PP), low-density polyethylene (LDPE) or polyacrylonitrile (PAN) as sealing layer.
  • PE polyethylene
  • PP polypropylene
  • LDPE low-density polyethylene
  • PAN polyacrylonitrile
  • PAN comprises polyacrylonitrile as well as copolymers of acrylonitrile units and one or more other monomers (AN-copolymers) such as acrylonitrile-methylacrylate copolymer.
  • blisters consisting of an aluminum push-through foil and a thermoplastic film are also available for packaging tablets.
  • Suitable thermoplastic films include thermoplastic composite films, which typically consist of multiple layers of different plastics, such as PE, PVC, PP, LDPE or PAN.
  • the mentioned packaging materials are also suitable for other kinds of dosage forms available for individual doses such as powders and orally fast dissolving films.
  • WO 01/068062 and WO 03/066472 describe packaging materials useful for transdermal drug delivery systems containing chiral drugs such as methylphenidate, and child resistant sachets having a sufficient tear resistance, respectively.
  • WO 03/066472 mentions that acrylonitrile-methylacrylate copolymer resins (e.g. Barex ® resins) are more difficult to be bonded by melt sealing than other materials, but have advantageous flavor barrier properties.
  • Barex ® resins are also known from the corresponding product information ("Barex ® Resins", INEOS Barex, USA, 2006 , retrieved from the Internet: URL:http://www.ineosbarex.com/files/upload/Ineos%20Barex%20Brochure.pdf on 2012-05-15).
  • the object of the present invention is to provide a solid pharmaceutical preparation containing GTN for oral and oromucosal (such as sublingual or buccal) administration in the form of individually packaged single doses having good storage stability.
  • a stable medicament comprising a solid pharmaceutical preparation containing the active substance GTN for oral or oromucosal administration in the form of one or more individual doses, wherein the one or more individual doses are packaged in aluminium composite films or thermoplastic blister films, which contain a layer comprising PAN on the side facing the preparation.
  • solid GTN-containing preparations remain stable for the required time period if they are packaged in composite films containing a layer comprising PAN on the surface facing the product.
  • Preferred are aluminum composite films containing a sealing layer comprising an acrylonitrile-methylacrylate copolymer, while aluminium composite films containing a sealing layer made of an impact-modified acrylonitrile-methylacrylate copolymer are particularly preferred.
  • barrier plastics are marketed, among others, under the commercial names Barex ® 210 or Barex ® 218.
  • the preparations according to the invention are packaged as individual doses which remain stable for a storage period of at least 6 months at 40 °C and 75 % relative humidity.
  • the preferred pharmaceutical preparation is an oromucosal, solid, GTN-containing preparation, preferably a GTN-containing, flowable powder or flowable granules, respectively, for sublingual administration, which may optionally be pressed into a sublingual tablet.
  • the pharmaceutical preparation contains 0.05 to 2 weight % GTN; GTN concentrations of 0.10, 0.20, 0.25, 0.30, 0.40, 0.50, 0.60, 0.70, 0.80, 1.0, 1.2, 1.4, 1.6 or 1.8 weight % are especially preferred. Unless otherwise stated, all weight percentages are based on the total weight of the preparation.
  • the pharmaceutical preparation according to the invention may contain one or more other pharmaceutical excipients, which support sublingual release of the active substance and which are selected from water-soluble mono-, di-, and polysaccharides, as well as their alcohols.
  • These excipients are especially selected from fructose, glucose, isomalt, lactose, maltitol, maltose, mannitol, saccharose, sorbitol, trehalose and xylitol, and mixtures thereof.
  • These excipients are preferably present in a total content of 90 to 98 weight %. In the case of mixtures, the concentration of each individual substance is 20 to 70 weight %, whereby the preferred contents include 25, 30, 35, 40, 45, 50, 55, 60 or 65 weight %.
  • the preparation according to the invention may optionally be provided with a coating.
  • the preparation according to the invention may contain other excipients, such as flavoring agents.
  • Flavoring agents are used especially in the case of preparations for oral or sublingual administration in order to increase acceptance among patients. According to the invention, they are preferably used at concentrations of 0.01 to 3.0 weight %, whereby the especially preferred concentrations include 0.5, 1, 1.5, 2 or 2.5 weight %.
  • GTN intended for pharmaceutical purposes is phlegmatized by the manufacturer, i.e. embedded in a matrix, which reduces the risk posed by the hazardous properties.
  • the matrix can be in liquid or in powder form.
  • GTN is available as a 5% solution in medium-chain triglycerides, such as Miglyol ® 812 or Miglyol ® 840, or propylene glycol, as a 10% lactose triturate or a 2.25% dilution in glucose. If these GTN concentrates are used for producing the pharmaceutical preparation according to the invention, the agent used for phlegmatization of GTN is regularly contained in the finished product. If GTN is phlegmatized in a volatile solvent like ethanol, the solvent can be lost during the production process.
  • GTN was used as a 5% concentrate in Miglyol ® 812. Unless otherwise stated, the optionally pre-granulated excipients were processed into a homogenous mixture with the GTN concentrate.
  • Example 1 The granules according to Example 1 were packaged in the packaging materials referred to in Examples 2 through 5 and stored for 12 weeks at 25°C and 60% relative humidity and at 40°C and 75% relative humidity. As a reference, granules were stored in open dishes and in glass containers.
  • PET - aluminum - 75 ⁇ m LDPE low-density polyethylene
  • PET - aluminum - 50 ⁇ m PAN (Barex ® 210)
  • the preparation according to the present invention can be supplied as individual dose, e.g. within a stick pack or sachet, wherein the aluminum composite film contains a layer comprising PAN on the side facing the preparation.
  • Single doses of GTN in form of tablets, pellets or capsules can likewise be filled in stick packs and sachets or packaged in blisters, whose thermoplastic film surface contains a layer comprising PAN on the side facing the preparation.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Nutrition Science (AREA)
  • Emergency Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Zoology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Mechanical Engineering (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Inorganic Chemistry (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Claims (15)

  1. Composition pharmaceutique solide comprenant du glyceryl trinitrate (GTN), sous la forme d'une dose unique pour administration par voie oromucosale ou par voie orale, qui est emballée dans un film composite, lequel film composite contient une couche comprenant du polyacrylonitrile (PAN) du côté faisant face à la composition pharmaceutique.
  2. Composition selon la revendication 1 où le film composite est un film composite en aluminium.
  3. Composition selon la revendication 1 où le film composite est un film composite thermoplastique.
  4. Composition selon l'une quelconque des revendications 1 à 3 où la couche du film composite du côté faisant face à la composition pharmaceutique comprend un copolymère d'acrylonitrile-methylacrylate.
  5. Composition selon la revendication 4 où la couche du film composite du côté faisant face à la composition pharmaceutique comprend un copolymère d'acrylonitrile-methylacrylate modifié par impact.
  6. Composition selon l'une quelconque des revendications 4 ou 5, où la couche du film composite du côté faisant face à la composition pharmaceutique comprend un copolymère d'acrylonitrile-methylacrylate modifié par impact.
  7. Composition selon l'une quelconque des revendications 1 à 6, caractérisée en ce qu'elle contient entre 0.05 et 2 % en masse de glyceryl trinitrate.
  8. Composition selon l'une quelconque des revendications 1 à 7 contenant au moins un autre excipient approprié pour une administration par voie sublinguale sélectionné parmi le fructose, le glucose, l'isomalt, le lactose, le maltitol, le maltose, le mannitol, le saccharose, le sorbitol, le trehalose et le xylitol, et leurs mélanges.
  9. Composition selon la revendication 8 contenant au moins un autre excipient approprié pour une administration par voie sublinguale, qui est le xylitol et/ou l'isomalt à des concentrations de 20 à 95 % en masse.
  10. Composition selon l'une quelconque des revendications précédentes contenant au moins un agent aromatisant.
  11. Composition selon l'une quelconque des revendications precedentes où GTN est formulé sous forme de granules.
  12. Composition selon l'une quelconque des revendications precedentes qui est emballée sous la forme d'une dose unique pour administration par voie oromucosale ou par voie orale.
  13. Composition selon l'une quelconque des revendications precedentes où la forme de dosage unique est contenue dans un sachet stick.
  14. Composition selon l'une quelconque des revendications 1 à 9 où le GTN est formulé sous la forme d'un comprimé.
  15. Composition selon l'une quelconque des revendications 1 à 9 où le GTN est formulé sous la forme d'un film à dissolution rapide par voie orale.
EP12706778.3A 2011-02-25 2012-02-24 Conditionnement de préparations pharmaceutiques solides contenant la substance active trinitrate de glycéryle Not-in-force EP2678006B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PL12706778T PL2678006T3 (pl) 2011-02-25 2012-02-24 Pakowanie stałych preparatów farmaceutycznych zawierających substancję aktywną triazotan glicerolu

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102011012491 2011-02-25
PCT/EP2012/000802 WO2012113563A1 (fr) 2011-02-25 2012-02-24 Conditionnement de préparations pharmaceutiques solides contenant la substance active trinitrate de glycéryle

Publications (2)

Publication Number Publication Date
EP2678006A1 EP2678006A1 (fr) 2014-01-01
EP2678006B1 true EP2678006B1 (fr) 2015-12-30

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Family Applications (3)

Application Number Title Priority Date Filing Date
EP12707232.0A Active EP2678000B1 (fr) 2011-02-25 2012-02-24 Granules stabilisés contenant du trinitrate de glycéryle
EP18159399.7A Withdrawn EP3354259A1 (fr) 2011-02-25 2012-02-24 Granules stabilisées contenant du trinitrate de glycéryl
EP12706778.3A Not-in-force EP2678006B1 (fr) 2011-02-25 2012-02-24 Conditionnement de préparations pharmaceutiques solides contenant la substance active trinitrate de glycéryle

Family Applications Before (2)

Application Number Title Priority Date Filing Date
EP12707232.0A Active EP2678000B1 (fr) 2011-02-25 2012-02-24 Granules stabilisés contenant du trinitrate de glycéryle
EP18159399.7A Withdrawn EP3354259A1 (fr) 2011-02-25 2012-02-24 Granules stabilisées contenant du trinitrate de glycéryl

Country Status (7)

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US (4) US20130331461A1 (fr)
EP (3) EP2678000B1 (fr)
AU (2) AU2012219926B2 (fr)
CA (2) CA2827714A1 (fr)
ES (2) ES2565632T3 (fr)
PL (2) PL2678000T3 (fr)
WO (2) WO2012113564A1 (fr)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2617494T3 (es) * 2012-05-31 2017-06-19 G. Pohl-Boskamp Gmbh & Co. Kg Inducción de arteriogénesis con un donador de óxido nítrico tal como nitroglicerina
WO2019009927A1 (fr) 2017-07-06 2019-01-10 Adorus Pharmaceuticals Llc Compositions de mélange pour administration orale en tant que poudre et/ou suspension à dissolution rapide

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US20130331461A1 (en) 2013-12-12
ES2565632T3 (es) 2016-04-06
US20130327676A1 (en) 2013-12-12
AU2012219926A1 (en) 2013-09-12
US9101592B2 (en) 2015-08-11
EP2678000A1 (fr) 2014-01-01
AU2012219925A1 (en) 2013-10-03
US9616023B2 (en) 2017-04-11
EP3354259A1 (fr) 2018-08-01
EP2678000B1 (fr) 2018-03-07
PL2678006T3 (pl) 2016-06-30
EP2678006A1 (fr) 2014-01-01
US20140370109A1 (en) 2014-12-18
AU2012219926B2 (en) 2016-11-17
CA2827714A1 (fr) 2012-08-30
WO2012113564A1 (fr) 2012-08-30
AU2012219925B2 (en) 2017-02-23
ES2672261T3 (es) 2018-06-13
WO2012113563A1 (fr) 2012-08-30
CA2827716A1 (fr) 2012-08-30
PL2678000T3 (pl) 2018-08-31
US20160000711A1 (en) 2016-01-07

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